The applicant organization, EKOS, has developed a drug delivery catheter device that utilizes low energy ultrasound to enhance drug-mediated thrombolysis. Despite the progress in animal studies and human trials, the underlying acoustic and biochemical mechanisms for the enhancement of thrombolysis are not fully understood. The applicants hypothesized ultrasound can enhance thrombolysis further than currently observed, but new experimental assays and models are needed in order to optimize the effects of the ultrasound and to better understand the fundamental mechanisms. In Phase II, the applicants proposed to continue to investigate acoustic mechanisms of thrombolysis and acoustic protocols that may further enhance thrombolysis by characterization of kinetic and transport parameters in well defined and controlled experiments. In addition, they proposed to focus on the mechanisms by which microbubbles further enhance the ultrasound-mediated thrombolytic process. This has been shown in vitro and in vivo but there is little understanding of how best to use microbubbles to maximize their synergistic effect with ultrasound in a therapeutic rather than diagnostic mode. These studies are critical to determining how the EKOS ultrasound catheter can be optimized for use in human patients as well as to provide insight into the development of future thrombolytic products. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE